Therapy of chronic hepatitis B (CHB) using oral antiviral agents has been shown to suppress viral replication. There are guidelines on when to start antiviral therapy but none on when to stop therapy once initiated. This study hinges on the argument that it is safe and desirable to endeavor to attain a durable off-treatment response (DOTR) to therapy in hepatitis B infected individuals with advanced liver fibrosis who have had complete and long-term viral suppression. Preliminary data demonstrate that a DOTR can be achieved and that it is rare to have adverse clinical outcomes after stopping therapy even in compensated cirrhotics if patients are closely monitored. This study is a formal test of the safety of structured treatment interruption (STI). Our plan is to evaluate Tenofovir (TDF) and Truvada in a multi-centre, double-blinded, placebo-controlled randomized trial of treatment-nave stable, well-compensated cirrhotics with HBV DNA =10 X 4 copies/mL. Specific aims are: 1) to test the safety and cost-effectiveness of an STI after 2 years vs 4 years duration of continuous and complete viral suppression (HBV DNA <70 copies/mL); 2) to test whether 4 years is superior to 2 years duration of continuous and complete suppression; 3) to identify if there are marked differences between TDF and Truvada; and 4) to determine if quantitative HBsAg levels, immune markers, or intrahepatic cccDNA levels can predict the likelihood of achieving a DOTR. In addition, we propose a clinical database structure which can facilitate clinical management while providing information on the epidemiology of CHB and the underlying socioeconomic, cultural, and clinical factors that contribute to outcomes in CHB. Electronic health records will feed serial clinical and laboratory data into the database. Clinical prompts will facilitate the need for urgent action with therapeutic interventions and deliver patient reminders for timely follow-up. The database will be used to examine how viral and host factors influence the development of liver-related complications in patients with advanced CHB. Results from this study could produce stopping rules for management guidelines, which would constitute a major advancement in the field.